Benzodiazepine Use in Pregnancy Linked to Higher Preterm Birth Risk, Large Study Finds
Taiwan: A large population-based study published in JAMA Internal Medicine has raised important safety considerations regarding benzodiazepine use during pregnancy, suggesting that these commonly prescribed medications may be linked to adverse birth outcomes when competing pregnancy risks are taken into account. The study was conducted by Brian Meng-Hsun Li from the Population Health Data Centre, National Cheng Kung University, Tainan, Taiwan, and colleagues.
Benzodiazepines are widely used to manage anxiety, insomnia, and other psychiatric conditions, and their use during pregnancy has increased in recent years. However, evidence on their safety has remained inconsistent, partly due to methodological limitations in earlier studies. In particular, prior analyses often focused only on live births, potentially overlooking the influence of abortion and stillbirth as competing pregnancy outcomes.
To address these gaps, the researchers analyzed data from Taiwan’s National Health Insurance Research Database, covering the period from 2011 to 2021. Using a target trial emulation framework, they evaluated 454,477 pregnancies among women aged 15 to 55 years who had no benzodiazepine use in the six months before pregnancy. The analysis compared pregnancy outcomes between benzodiazepine users and nonusers across gestational weeks 0 to 36, with careful adjustment for confounding factors and competing events.
Key Findings:
- Analyses limited to live births initially suggested that benzodiazepine exposure was associated with lower risks of preterm birth and small-for-gestational-age infants.
- This apparent protective association changed after abortion and stillbirth were included as competing outcomes.
- Benzodiazepine use was associated with a significantly higher risk of abortion, including both spontaneous and elective terminations.
- No meaningful association was observed between benzodiazepine exposure and stillbirth.
- After accounting for competing risks, benzodiazepine exposure was linked to an increased risk of preterm birth.
- A modest increase in the risk of small for gestational age was also observed after adjustment, though this association was sensitive to the analytic method.
- The increased risks were most pronounced with benzodiazepine exposure during the second trimester, suggesting a critical period of fetal vulnerability.
The authors emphasized that analyses limited to live births may underestimate harm due to selective survival bias, as pregnancies with poorer outcomes may end earlier and therefore be excluded. By incorporating competing events, the study provides a more comprehensive assessment of risk and helps reconcile conflicting findings from previous research.
While the investigators applied robust statistical techniques, including inverse probability weighting and high-dimensional propensity score methods, they acknowledged several limitations. Residual confounding cannot be completely excluded; some early abortions may not have been captured in the database, and exposure timing was assessed in weekly rather than daily intervals, which could introduce minimal bias.
Overall, the findings suggest that benzodiazepine use during pregnancy is associated with an increased risk of preterm birth and may also modestly increase the risk of restricted fetal growth when competing pregnancy outcomes are considered. The authors urge clinicians to interpret the results cautiously and carefully weigh potential benefits against risks when prescribing benzodiazepines to pregnant patients, emphasizing the importance of individualized clinical decision-making and close monitoring.
Reference:
Li BM, Wei S, Chuang M, Lai EC. Benzodiazepine Use in Pregnancy and the Risk of Pregnancy Outcomes. JAMA Intern Med. Published online December 22, 2025. doi:10.1001/jamainternmed.2025.6882
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